Kalra P S, Sahu A, Bonavera J J, Kalra S P
Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville 32610.
Endocrinology. 1992 Sep;131(3):1195-201. doi: 10.1210/endo.131.3.1380435.
The tachykinins are a group of structurally related peptides found in the rat hypothalamus and anterior pituitary. We have evaluated the effects of four tachykinins on LH release in male rats. In intact male rats, intracerebroventricular (icv) injection of neurokinin A (NKA), neuropeptide K (NPK), and neuropeptide-gamma (NP gamma) elicited dose-related, transient increases in plasma LH. Substance P (SP) was ineffective under these conditions. A further examination showed that in vitro incubation with either NPK or NP gamma of hemipituitaries from intact but not castrated male rats promoted release of LH into the medium, thereby revealing that the excitatory effects of tachykinins in intact male rats may, in part, be a result of stimulation of LH release directly from the anterior pituitary. On the other hand, the effects of these four tachykinins on LH release were different in castrated rats. Intracerebroventricular injection of NPK, NKA, and NP gamma as well as SP, which was ineffective in intact male rats, evoked a long-lasting suppression of LH release. Comparatively, NPK was the most effective tachykinin in eliciting LH responses in both of these tests involving different endocrine environments. We next evaluated the possibility that the inhibitory effects of tachykinins (NPK) may be mediated by activation of inhibitory endogenous opioid peptides. The results showed that iv infusion of the opiate receptor antagonist naloxone, to block the possible inhibitory effects of endogenous opioid peptides, only partially counteracted the suppressive effects of icv NPK on plasma LH levels. Thus, in addition to revealing the diverse effects of structurally related tachykinins on LH release, the results of these investigations showed specifically that the NK-2 receptor agonists NPK, NP gamma, and NKA stimulated LH release in intact rats, in part, by a direct action at the level of the pituitary, whereas the NK-1 receptor agonist SP was inactive under these conditions. These findings imply a paracrine/autocrine mode of excitatory action on LH release involving pituitary NK-2 receptor subtypes. On the other hand, in castrated rats, all four tachykinins readily suppressed LH release by a central action involving, in part, an activation of hypothalamic opioid systems.
速激肽是在大鼠下丘脑和垂体前叶中发现的一组结构相关的肽。我们评估了四种速激肽对雄性大鼠促黄体生成素（LH）释放的影响。在完整的雄性大鼠中，脑室内（icv）注射神经激肽A（NKA）、神经肽K（NPK）和神经肽γ（NPγ）会引起血浆LH剂量相关的短暂升高。在这些条件下，P物质（SP）无效。进一步的研究表明，在体外，用NPK或NPγ孵育完整但未阉割的雄性大鼠的半垂体可促进LH释放到培养基中，从而表明速激肽在完整雄性大鼠中的兴奋作用可能部分是直接刺激垂体前叶释放LH的结果。另一方面，这四种速激肽对阉割大鼠LH释放的影响不同。脑室内注射NPK、NKA和NPγ以及在完整雄性大鼠中无效的SP，均可引起LH释放的长期抑制。相比之下，在这两种涉及不同内分泌环境的试验中，NPK是引发LH反应最有效的速激肽。接下来，我们评估了速激肽（NPK）的抑制作用可能由内源性阿片肽激活介导的可能性。结果表明，静脉输注阿片受体拮抗剂纳洛酮以阻断内源性阿片肽的可能抑制作用，仅部分抵消了脑室内注射NPK对血浆LH水平的抑制作用。因此，这些研究结果除了揭示结构相关的速激肽对LH释放的多种作用外，还特别表明NK - 2受体激动剂NPK、NPγ和NKA在完整大鼠中部分通过直接作用于垂体水平刺激LH释放，而NK - 1受体激动剂SP在这些条件下无活性。这些发现意味着对LH释放存在一种旁分泌/自分泌兴奋作用模式，涉及垂体NK - 2受体亚型。另一方面，在阉割大鼠中，所有四种速激肽都通过一种中枢作用轻易地抑制LH释放，这种中枢作用部分涉及下丘脑阿片系统的激活。
